Sequence and in vitro function of chicken, ring-necked pheasant, and Japanese quail AHR1 predict in vivo sensitivity to dioxins

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

46 Scopus Citations
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Author(s)

  • Reza Farmahin
  • Dongmei Wu
  • Doug Crump
  • Jessica C. Hervé
  • Stephanie P. Jones
  • And 6 others
  • Mark E. Hahn
  • Sibel I. Karchner
  • John P. Giesy
  • Steven J. Bursian
  • Matthew J. Zwiernik
  • Sean W. Kennedy

Detail(s)

Original languageEnglish
Pages (from-to)2967-2975
Journal / PublicationEnvironmental Science and Technology
Volume46
Issue number5
Publication statusPublished - 6 Mar 2012

Abstract

There are large differences in sensitivity to the toxic and biochemical effects of dioxins and dioxin-like compounds (DLCs) among vertebrates. Previously, we demonstrated that the difference in sensitivity between domestic chicken (Gallus gallus domesticus) and common tern (Sterna hirundo) to aryl hydrocarbon receptor 1 (AHR1)-dependent changes in gene expression following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is based upon the identities of the amino acids at two sites within the ligand binding domain of AHR1 (chicken - highly sensitive; Ile324-Ser380 vs common tern - 250-fold less sensitive than chicken; Val325-Ala381). Here, we tested the hypotheses that (i) the sensitivity of other avian species to TCDD, 2,3,4,7,8- pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) is also determined by the amino acids at sites that are equivalent to sites 324 and 380 in chicken, and (ii) Ile324-Ala380 and Val324-Ser380 genotypes confer intermediate sensitivity to DLCs in birds. We compared ligand-induced transactivation function of full-length AHR1s from chicken, common tern, ring-necked pheasant (Phasianus colchicus; Ile324-Ala380) and Japanese quail (Coturnix japonica; Val324-Ala380), and three Japanese quail AHR1 mutants. The results support our hypothesis that avian species can be grouped into three general classes of sensitivity to DLCs. Both AHR1 genotype and in vitro transactivation assays predict in vivo sensitivity. Contrary to the assumption that TCDD is the most potent DLC, PeCDF was more potent than TCDD at activating Japanese quail (13- to 26-fold) and common tern (23- to 30-fold) AHR1. Our results support and expand previous in vitro and in vivo work that demonstrated ligand-dependent species differences in AHR1 affinity. The findings and methods will be of use for DLC risk assessments. © 2012 American Chemical Society.

Citation Format(s)

Sequence and in vitro function of chicken, ring-necked pheasant, and Japanese quail AHR1 predict in vivo sensitivity to dioxins. / Farmahin, Reza; Wu, Dongmei; Crump, Doug; Hervé, Jessica C.; Jones, Stephanie P.; Hahn, Mark E.; Karchner, Sibel I.; Giesy, John P.; Bursian, Steven J.; Zwiernik, Matthew J.; Kennedy, Sean W.

In: Environmental Science and Technology, Vol. 46, No. 5, 06.03.2012, p. 2967-2975.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review